The long term objective of this research is to obtain a molecular picture of the nature of T cell recognition of cell surface molecules encoded in the Major Histocompatibility Complex (MHC) and foreign antigen. Our approach is to use retrovirus vectors to transfer and express T cell receptors in immunocompetent cells. Viruses which express the T cell receptor alpha and beta chains and two different selectable markers will be used to infect functional T cells. We will determine whether the specificity for antigen and MHC is conferred by the expression of these two chains. Gene transfer of T cell receptors will also be used to examine the phenomenon of alloreactivity and how it is encoded by T cell receptor sequences. We also intend to use the unique properties of retrovirus vectors to facilitate a genetic approach to the analysis of the function of T cell receptors by mutagenesis. Random mutagenesis will be used to generate a map of the regions that encode the functional reactivities of the T cell receptor. It is anticipated that the knowledge of the molecular structures involved in MHC restriction will provide a basis for understanding the linkage of MHC genes to various diseases and the T cell immune response.